We propose to study three systems of antigens of special interest which are expressed on epidermal cells: (1) SK: Sk ("Skin") antigens are confined to brain and epidermal cells. By a new serological test, and further genetic analysis, we intend to ascertain in more detail the role of Sk antigens in tissue-selective homograft rejection and to identify the Sk genetic locus or loci responsible for their expression. Availability of a cytotoxicity test for Sk antigens, and prospects of a more sensitive serological test, are critical to this work. (2) H(Tla): This new H locus causes skin graft rejection between Tl congenic crossover strains, and must map near Tla in Linkage Group IX. We intend to locate H(Tla) in relation to Tla, to seek evidence of multiple H(Tla) alleles, to distinguish the H effects of H-2(D) antigens from those of H(Tla), and to investigate a serological test system for H(Tla). (3) H- Y: Recent development of a cytotoxicity test for male-specific H-Y antigen offers a more feasible and rigorous approach to questions about this important system. Using the cytotoxicity assay, and a new assay based on binding of sheep red cells via a hybrid antibody, we shall study the specificity of H-Y antigens in males of various species. We shall also compare the H-Y antibody responses of female mice that naturally fail to reject male skin with those of females whose capacity to reject male skin has been abrogated by grafting of male neonatal skin, to see whether these two unresponsive states may be similar or different.